(a) Field of the Invention
The present invention relates to novel polypeptides which are useful as pharmaceuticals etc. and production thereof.
.gamma.-interferon (hereinafter also referred to as IFN-.gamma.) is produced by immunocompetent cells under the same condition as those promoting lymphocyte blastogenesis and lymphokine production, thus it is also named immune interferon. IFN-.gamma.is reported to be higher in cell proliferation inhibitory activity and antitumor activity than IFN-.alpha.and IFN-.alpha.; it is expected that this type of interferon will work well in clinical application. At present, however, there is no efficient process for its production because these are some drawbacks involved, e.g., its production requires the supply of fresh lymphocytes.
As a result of the application of gene recombination technology, however, the nucleotide sequence and amino acid sequence (deduced from the former) of the complementary DNA (cDNA) of IFN-.gamma. have recently been clarified by cloning the cDNA; it has also become possible to make cDNA and chemically synthesized genes express themselves using various host species [Gray, P.W. et al., Nature, 295, 503 (1982); Debos, R. et al., Nucleic Acids Research, 10, 2487 (1982); Tanaka, S. et al., Nucleic Acids Research, 11, 1707 (1983)].
Gray et al. [Nature, 295, 503 (1982)] and Derynck et al. [Nucleic Acids Research, 10, 3605 (1982)] refer to a peptide composed of 146 amino acid molecules as IFN-.gamma.. The same amino acid numbers as those in the above-mentioned references are used in the present specification (refer to FIG. 4).
It has also become possible to mass-produce IFN-.gamma. obtained via gene recombination (hereinafter also referred to as rIFN-.gamma.) using monoclonal antibodies [EP Patent Publication No. 0103898].
Many attempts have been made to delete, from the amino acid sequence of IFN-.gamma., partial amino acid sequences which are not though to be directly related to the bioactivity of IFN-.gamma..
For example, Japanese Patent Laid-open No. 202899/1985 which corresponds to EPC Patent Publication No. 146354 discloses amino acid sequences resulting from either the deletion of the N-terminal peptide chain ##STR1## in IFN-.gamma. or the deletion of an amino acid sequence of peptide composed of 1 to 17 amino acid molecules starting from the C-terminal in the C-terminal peptide chain ##STR2## of IFN-.gamma..
In addition, Japanese Patent Laid-open No. 233100/1985 which corresponds to EP Patent Publication No. 161504 discloses partial amino acid sequences of IFN-.gamma.: 5 to 127, 1 to 127 and 5 to 146. Of the three, however, the amino acid sequence 5 to 127 does not express itself as a polypeptide, though the DNA for peptide expression is constructed.
Japanese Patent Laid-open No. 5096/1986 which corresponds to EP Patent Publication No. 166993 discloses amino acid sequences resulting from the deletion of the N-terminal amino acid sequence Cys-Tyr, Cys-Tyr-Cys or Cys-Tyr-Cys-Gln in IFN-.gamma. and the deletion of an amino acid sequence or a peptide composed of 1 to 16 amino acid molecules starting from the C-terminal in the C-terminal peptide chain ##STR3## of IFN-.gamma..